1.Huoxue Anxin Recipe () promotes myocardium angiogenesis of acute myocardial infarction rats by up-regulating miR-210 and vascular endothelial growth factor.
Jie WANG ; Yun ZHANG ; Yong-Mei LIU ; Li-Li GUO ; Ping WU ; Yu DONG ; Guang-Jun WU
Chinese journal of integrative medicine 2016;22(9):685-690
OBJECTIVETo investigate the microRNAs (miRNAs) expression profile of acute myocardial infarction (AMI) rats and the regulating effects of Huoxue Anxin Recipe (, HAR) on angiogenesis-related miRNAs and genes.
METHODSForty-five Wistar rats were randomly assigned to 3 groups according to a random number table: sham, AMI, and AMI+HAR groups (15 in each group). AMI rats were established by ligation of the left descending coronary artery. HAR was intragastrically administered to rats of the AMI+HAR group for successive 21 days since modeling, meanwhile the same volume of 0.9% normal saline was administered to rats of the sham and AMI groups. Doppler echocardiography was used for noninvasive cardiac function test. Hematoxylin and eosin staining was used to observe the histopathological change. miRNAs expression profile was detected by quantitative realtime polymerase chain reaction (qRT-PCR). The mRNA and protein expressions of vascular endothelial growth factor (VEGF), and a target gene of miR-210 was further detected by qRT-PCR and Western blot, respectively. The microvessels density of myocardium was evaluated by CD31 immunostaining.
RESULTSCompared with the sham group, ejection fraction (EF) and fractional shortening (FS) values were decreased significantly in the AMI group (P<0.01), while the infarction area and the interstitial collagen deposition were increased obviously. As for the AMI+HAR group, EF and FS values were increased significantly (P<0.05 vs. AMI group), and the infarction area was reduced and the interstitial collagen deposition were alleviated significantly. Total of 23 miRNAs in the AMI group expressed differently by at least 1.5 folds compared with those in the sham group; 5 miRNAs in the AMI+HAR group expressed differently by at least 1.5 folds compared with those in the AMI group. Among them, miR-210 was low in the AMI group and high in the AMI+HAR group. The relative mRNA and protein expressions of VEGF were decreased significantly in the AMI group (P<0.05 vs. sham group), and increased significantly in the AMI+HAR group (P<0.01 vs. AMI group). CD31 expression area and optical intensity were decreased significantly in the AMI group (P<0.05 vs. sham group), and increased significantly in the AMI+HAR group (P<0.01 vs. AMI group).
CONCLUSIONSHAR could reduce the infarction area, alleviate the interstitial fibrosis and improve the cardiac function of AMI rats. Those effects could be related to promoting myocardium angiogenesis of HAR by up-regulating miR-210 and VEGF.
Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Heart Function Tests ; Male ; MicroRNAs ; genetics ; metabolism ; Microvessels ; pathology ; Myocardial Infarction ; drug therapy ; genetics ; physiopathology ; Myocardium ; pathology ; Neovascularization, Physiologic ; drug effects ; genetics ; RNA, Messenger ; genetics ; metabolism ; Rats, Wistar ; Up-Regulation ; drug effects ; Vascular Endothelial Growth Factor A ; genetics ; metabolism
2.Inhibition of Janus activated kinase-3 protects against myocardial ischemia and reperfusion injury in mice.
Young Bin OH ; Min AHN ; Sang Myeong LEE ; Hyoung Won KOH ; Sun Hwa LEE ; Suhn Hee KIM ; Byung Hyun PARK
Experimental & Molecular Medicine 2013;45(5):e23-
Recent studies have documented that Janus-activated kinase (JAK)-signal transducer and activator of transcription (STAT) pathway can modulate the apoptotic program in a myocardial ischemia/reperfusion (I/R) model. To date, however, limited studies have examined the role of JAK3 on myocardial I/R injury. Here, we investigated the potential effects of pharmacological JAK3 inhibition with JANEX-1 in a myocardial I/R model. Mice were subjected to 45 min of ischemia followed by varying periods of reperfusion. JANEX-1 was injected 1 h before ischemia by intraperitoneal injection. Treatment with JANEX-1 significantly decreased plasma creatine kinase and lactate dehydrogenase activities, reduced infarct size, reversed I/R-induced functional deterioration of the myocardium and reduced myocardial apoptosis. Histological analysis revealed an increase in neutrophil and macrophage infiltration within the infarcted area, which was markedly reduced by JANEX-1 treatment. In parallel, in in vitro studies where neutrophils and macrophages were treated with JANEX-1 or isolated from JAK3 knockout mice, there was an impairment in the migration potential toward interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), respectively. Of note, however, JANEX-1 did not affect the expression of IL-8 and MCP-1 in the myocardium. The pharmacological inhibition of JAK3 might represent an effective approach to reduce inflammation-mediated apoptotic damage initiated by myocardial I/R injury.
Animals
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Apoptosis/drug effects
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Cell Movement/drug effects
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Chemokines/pharmacology
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Heart Function Tests/drug effects
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Inflammation/pathology
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Janus Kinase 3/*antagonists & inhibitors/metabolism
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Macrophages/drug effects/metabolism/pathology
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Male
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Mice
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Mice, Inbred C57BL
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Myocardial Reperfusion Injury/drug therapy/*enzymology/physiopathology/*prevention & control
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Myocardium/enzymology/pathology
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Myocytes, Cardiac/drug effects/metabolism/pathology
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Neutrophils/drug effects/metabolism/pathology
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Quinazolines/pharmacology/therapeutic use
3.Protective effect of Chinese herbs for supplementing qi, nourishing yin and activating blood circulation on heart function of patients with acute coronary syndrome after percutaneous coronary intervention.
Hong-ying LIU ; Wei WANG ; Da-zhuo SHI ; Jun-bo GE ; Lei ZHANG ; Juan PENG ; Cheng-long WANG ; Pei-li WANG
Chinese journal of integrative medicine 2012;18(6):423-430
OBJECTIVETo investigate the effects of Chinese herbs for supplementing qi, nourishing yin and activating blood circulation on heart function of patients with acute coronary syndrome (ACS) after successful percutaneous coronary intervention (PCI).
METHODSOne hundred patients with ACS after successful PCI were randomly assigned to a Western medicine (WM) treatment group (WMG) and a combined treatment group (CMG) treated by Chinese herbs for supplementing qi, nourishing yin and activating blood circulation, besides Western medicine treatment, with 50 cases in each group. Both treatment courses were 6 months. The followup was scheduled at baseline, 6 months and 1 year after PCI, and New York Heart Association (NYHA) functional class, Chinese medicine (CM) symptom scores, blood stasis syndrome scores, and major adverse cardiovascular events (MACE) were observed, serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and hyper-sensitivity C-reactive protein (Hs-CRP) were measured, an echocardiogram was conducted to examine left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), inter-ventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), and ventricular wall motion index (VWMI).
RESULTSCompared with the baseline, LVEF significantly increased (P<0.01), and CM symptom scores, blood stasis syndrome scores, VWMI, LVEDV, LVESV, NT-proBNP, and Hs-CRP all decreased (P<0.01) in both groups at 6 months and at 1 year after PCI. There were no significant differences in all the above parameters at 1 year vs those at 6 months after PCI (P>0.05). VWMI, LVEDV, LVESV, NT-proBNP, Hs-CRP, LVEF, and CM symptom and blood stasis syndrome scores were all improved obviously in CMG than those in WMG (P<0.05 or P<0.01) at 6 months and at 1 year after PCI. There were no significant differences in NYHA functional class between CMG and WMG at different follow-up timepoints; it was notable that value was 0.054 when comparing the cases of NYHA functional class between the two groups at 1-year follow-up. During the 1-year follow-up, 3 MACE and 11 MACE occurred in CMG and WMG, respectively; the MACE rate in CMG was lower than that in WMG (6% vs 22%, P<0.05).
CONCLUSIONChinese herbs for supplementing qi, nourishing yin and activating blood circulation could improve heart function, reduce the CM symptom scores and blood stasis syndrome scores, and decrease the incidence of MACE in patients with ACS after successful PCI.
Acute Coronary Syndrome ; blood ; drug therapy ; physiopathology ; surgery ; C-Reactive Protein ; metabolism ; Cardiotonic Agents ; adverse effects ; pharmacology ; therapeutic use ; China ; epidemiology ; Coronary Circulation ; drug effects ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; therapeutic use ; Female ; Heart Function Tests ; drug effects ; Humans ; Incidence ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; New York ; Peptide Fragments ; blood ; Percutaneous Coronary Intervention ; adverse effects ; Postoperative Complications ; epidemiology ; etiology ; Qi ; Societies, Medical ; Syndrome ; Ultrasonography ; Yin-Yang
4.Effects of tetramethylpyrazine on cardiac function and mortality rate in septic rats.
Li-Heng GUO ; Cheng YANG ; Lei WANG ; Quan-Fu CHEN ; Ya-Nan HU ; Min-Zhou ZHANG
Chinese journal of integrative medicine 2012;18(8):610-615
OBJECTIVETo study the effects of tetramethylpyrazine (TMP) on cardiac function and mortality rate in septic rats.
METHODSFifty male Sprague-Dawley rats were randomized into a sham-operation group (sham group, n=10), normal saline group (NS group, n=20), and TMP group (n=20). The rats in the NS and TMP groups underwent cecal ligation and puncture (CLP) to induce sepsis. Rats in the NS group were injected with NS (10 mL/kg) immediately after CLP and 6 h after CLP. Rats in the TMP group were injected with TMP (10 mg/kg) at the same time points. Twenty-four hours after modeling, the mortality rates were observed in each group. Cardiac function and serum concentration of tumor necrosis factor α (TNF-α) were also tested. The correlation between TNF-α and the ejection fraction (EF) was observed. Left ventricle specimens were reserved for histomorphologic study.
RESULTSCompared with the sham group, the NS and TMP groups had decreased EF values and increased mortality rates and serum TNF-α levels (P <0.05). The TMP group had a comparatively lower mortality rate and TNF-α level and a higher EF value compared with the NS group (P <0.05). Histomorphology indicated that myocardial inflammation in the TMP group was mild compared with that in the NS group. There was a negative correlation between TNF-α level and EF value (r=-0.583,P=0.000).
CONCLUSIONTMP could reduce the mortality rate of septic rats and had certain protective effects on cardiac function.
Animals ; Heart Function Tests ; drug effects ; Male ; Myocardium ; pathology ; ultrastructure ; Pyrazines ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Sepsis ; blood ; diagnostic imaging ; drug therapy ; physiopathology ; Stroke Volume ; drug effects ; Survival Analysis ; Tumor Necrosis Factor-alpha ; blood ; Ultrasonography
5.Effect of xinfeng capsule on the cardiac function in patients with rheumatoid arthritis.
Yun-xiang CAO ; Jian LIU ; Yan ZHU
Chinese journal of integrative medicine 2011;17(10):738-743
OBJECTIVETo study the changes in cardiac function of rheumatoid arthritis (RA) patients and: to observe the effect of xinfeng capsule ( XFC) on them.
METHODSSixty-eight RA patients were: randomly assigned to two groups by a lottery: 38 patients in the treatment group treated orally with XFC, 3 capsules, thrice a day, and 30 in the control group treated with fengshi gutong capsule (FSGTC), 4 capsules, twice a day, 30 days as one course of treatment, and two courses were given for both groups. A normal control (NC) group including 20 healthy subjects was set up. The clinical efficacy was compared between the two treated groups. The changes in cardiac function, including early diastolic peak flow velocity (E), late diastolic peak flow velocity (A), left ventricular fraction shortening (FS), and E/A, as well as uric acid (UA), erythrocyte sedimentation rate (ESR), α-acid glycoprotein (α-AGP), and hypersensitive C-reaction protein (hs-CRP), were observed. The regulation T cell was determined with flow cytometry.
RESULTS(1) The total effective rate in the treatment group and the control group was 92.1%: (35/38) and 70.0% (21/30), respectively. Significant difference was shown between them (P<0.05). (2) CONCLUSIONSThe descendent of cardiac function exists in RA patients. XFC could improve cardiac: function of RA patients, which is superior to FSGTC. Its mechanism may be related to its effect on raising CD4 CD4(+)CD25 CD25(+)Treg and CD4 CD4(+)CD25 CD25(+)CD127(-) Treg cells, decreasing UA, α-AGP, and hs-CRP levels, reducing immune inflammation, adjusting the overall balance of immune response, and thus improving the cardiac function of RA patients.
Adult
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Aged
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Arthritis, Rheumatoid
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drug therapy
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physiopathology
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Capsules
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Drugs, Chinese Herbal
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pharmacology
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therapeutic use
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Female
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Heart Function Tests
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drug effects
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Humans
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Male
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Middle Aged
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Treatment Outcome
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Young Adult
6.Intervention of astragalus injection on the kidney injury after cardiopulmonary bypass of infants with congenital heart disease.
Yun-xing TI ; Zheng-xia PAN ; Chun WU
Chinese Journal of Integrated Traditional and Western Medicine 2011;31(5):631-634
OBJECTIVETo study the intervention of astragalus injection in the kidney injury of infants with congenital heart disease after cardiopulmonary bypass, thus providing a new method for protection of the kidney injury in them.
METHODSForty infants undergoing cardiac surgery with cardiopulmonary bypass were randomly assigned to the test group and the control group, twenty in each group. Astragalus Injection (at the dose of 2 mL/kg) was added in the perfusion fluid before giving to infants in the test group before bypass, while the normal saline of the same volume was added in the perfusion fluid before giving to infants in the control group (P < 0.01). The concentrations of serum tumor necrosis factor-alpha (TNF)-alpha, interleukin-6 (IL-6), cystatin C (CysC), and N-acetyl-beta-D-glucosaminidase (NAG) were detected with ELISA at the following time points, i.e., before bypass (T1), by the end of the surgery (T2), 2 h after surgery (T3), 6 h after surgery (T4), and 24 h after surgery (T5).
RESULTSThe serum CysC concentrations were not significantly higher after CPB (P > 0.05). The urinary NAG level increased significantly in the control group after surgery (P < 0.05), but no obvious increase of the urinary NAG level was found in the test group after surgery (P > 0.05). It was obviously lower than that of the control group (P < 0.05). After CPB serum TNF-alpha and IL-6 levels increased significantly in the control group (P < 0.05), while they were lower in the test group than in the control group (P < 0.01).
CONCLUSIONSCPB may result in the renal tubular injury in infants with congenital heart disease. The application of Astragalus Injection before the CPB plays a role in protecting renal tubular functions.
Acetylglucosaminidase ; urine ; Astragalus Plant ; Cardiopulmonary Bypass ; adverse effects ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Heart Defects, Congenital ; blood ; drug therapy ; urine ; Humans ; Infant ; Interleukin-10 ; blood ; Kidney Function Tests ; Male ; Phytotherapy ; Postoperative Period ; Tumor Necrosis Factor-alpha ; blood
7.Effect of Yiqi Bufei recipe see text on patients with pulmonary incompetence after pneumonectomy.
Yong YANG ; You-kui SHEN ; Xing-ming ZHOU ; Xiao-qing FU ; Wei-min MAO ; Li-wen DONG ; Jun WANG ; Gen-miao CHENG
Chinese journal of integrative medicine 2011;17(12):898-902
OBJECTIVETo study the effect of Yiqi Bufei Recipe ([see text], YBR) on surgical tolerability, pulmonary compensatory function and post-operation rehabilitation in patients with pulmonary incompetence (PI) after pneumonectomy.
METHODSYBR intervention was applied to 60 patients with PI after pneumonectomy (as test group), the pulmonary and cardiac functions changes before and after operation, occurrence of postoperative complications, mortality, and the number of hospitalization days and intensive care unit (ICU) confinement period were observed. Meantime, for the negative and positive controls, the same parameters were observed comparatively in 60 patients with normal lung function, and in 60 patients with PI undergoing a similar operation but untreated with Chinese herbs.
RESULTSLung function in the test group showed insignificant change before and after operation (P >0.05), while significant decrease was seen in the two control groups (P<0.05). Furthermore, the incidences of post-operation complications and mortality as well as the number of hospitalization days and the ICU confinement period in the test group were significantly lower than those in the positive control group respectively (P <0.05).
CONCLUSIONYBR could relieve lung injury after pneumonectomy, improve surgical tolerability, reduce the length of postoperative hospitalization days and ICU confinement period, and lower the incidence of postoperative complications and mortality in patients with PI after pneumonectomy.
Blood Gas Analysis ; China ; epidemiology ; Drugs, Chinese Herbal ; pharmacology ; Female ; Heart Function Tests ; drug effects ; Humans ; Incidence ; Intensive Care Units ; Length of Stay ; Lung ; drug effects ; physiopathology ; surgery ; Male ; Middle Aged ; Pneumonectomy ; adverse effects ; Postoperative Complications ; epidemiology ; etiology ; Respiratory Function Tests ; Treatment Outcome
8.Clinical effect of Astragalus granule of different dosages on quality of life in patients with chronic heart failure.
Qing-You YANG ; Shu LU ; Hui-Ru SUN
Chinese journal of integrative medicine 2011;17(2):146-149
OBJECTIVETo explore the dose-effect relationship of Astragalus granule (AG) on improving the quality of life (QOL) of the patients with chronic heart failure (CHF).
METHODSNinety CHF patients of Fei ()-qi-deficiency and/or Xin ()-Shen () yang-deficiency syndromes were equally randomized divided with a random number table into three groups; they received the high (7.5 g), moderate (4.5 g), and low dosage (2.25 g) of AG orally taken twice a day, respectively, and 4 mg of perindopril tablet once a day for 30 successive days. The heart function grade, patients' left ventricular ejection fraction (LVEF) and walking distance in 6 min (6mWD) were measured before and after treatment, and the patients' QOL was scored by the Minnesota Questionnaire for QOL evaluation in the patients with CHF at the same time.
RESULTSThe heart function grades of all the three groups after treatment were improved compared with those before treatment, but the improvements in high-dose group and moderate dose group were better than that in the low dose group (P<0.05). LVEFs were increased significantly in all the three groups, but the improvements in the high-dose group (59.42%±7.50%) and moderate dose group (61.98%±6.82%) were better than that in the low dose group (51.45%±6.80%, P<0.01); the 6mWDs in the all groups were also significantly increased (P<0.01), up to 419.80±36.23 m, 387.15±34.13 m, and 317.69±39.97 m, respectively; and Minnesota scores in them were lowered to 29.59±4.69 scores, 35.74±5.89 scores, and 42.78±6.06 scores, respectively; comparisons in aspects on 6mWD and Minnesota score showed that the effectiveness with high dose is the most effective, moderate dose as the second, and low dose as the lowest (P<0.01).
CONCLUSIONSAG was sufficient to display an optimal effect on improving heart contraction at the moderate dose. In aspects of improving the QOL of CHF patients, the effectiveness of AG showed a dose-dependent trend. It should be applied discriminatively depending on the actual condition of patients and the aim of treatment in clinic.
Aged ; Astragalus Plant ; chemistry ; Chemistry, Pharmaceutical ; Chronic Disease ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Heart ; drug effects ; physiology ; Heart Failure ; drug therapy ; psychology ; Heart Function Tests ; Humans ; Male ; Middle Aged ; Plant Preparations ; administration & dosage ; Quality of Life ; Treatment Outcome ; Ventricular Function, Left ; drug effects ; physiology
9.Propofol improves cardiac functional recovery after ischemia-reperfusion by upregulating nitric oxide synthase activity in the isolated rat hearts.
Hai-Yan SUN ; Fu-Shan XUE ; Ya-Chao XU ; Cheng-Wen LI ; Jun XIONG ; Xu LIAO ; Yan-Ming ZHANG
Chinese Medical Journal 2009;122(24):3048-3054
BACKGROUNDThere are few studies to assess whether propofol attenuates myocardial ischemia-reperfusion injury via a mechanism related to nitric oxide (NO) route, so we designed this randomized blinded experiment to observe the changes of NO contents, nitric oxide synthase (NOS) activity, NOS contents in the myocardium, and cardiac function in ischemic reperfused isolated rat hearts, and to assess the relation between myocardial NO system and cardioprotection of propofol.
METHODSThe hearts of 30 Sprague-Dawley male rats were removed, mounted on a Langendorff apparatus, and randomly assigned to one of three groups (n = 10 each group) to be treated with the following treatments in a blinded manner: Group 1, control group, after perfusion with pure Krebs Henseleit bicarbonate (K-HBB) buffer solution for 15 minutes, hearts were subjected to 20 minutes global ischemia followed by 60 minutes reperfusion with pure K-HBB buffer; Group 2, after perfusion with K-HBB buffer solution containing propofol (10 microg/ml) for 15 minutes, the hearts underwent 20 minutes global ischemia followed by 60 minutes reperfusion with the same K-HBB buffer solution; Group 3, after perfusion with K-HBB buffer solution containing propofol (10 microg/ml) and L-NAME (100 micromol/L) for 15 minutes, the hearts underwent 20 minutes global ischemia followed by 60 minutes reperfusion with the same K-HBB buffer solution. The cardiac function was continuously monitored throughout the experiment. The coronary flow was also measured. An ISO-NO electrode was placed into the right atrium close to the coronary sinus to continuously measure NO concentration in the coronary effluent. The tissue samples from apex of hearts in Groups 1 and 2 were obtained to measure the NOS activity by spectrophotometry and the NOS contents by immunohistochemistry, respectively.
RESULTSThe cardiac function was significantly inhibited after ischemia and then gradually improved with reperfusion in all three groups. As compared with Group 1, the cardiac function variables and coronary flow at all the observed points were significantly improved in Group 2. The cardiac function variables and coronary flow were better in Group 3 than in Group 1, but were inferior in Group 3 than in Group 2. Both NO contents and NOS activity in the myocardium were significantly higher in Group 2 than in Group 1. However, NOS contents in the myocardium did not significantly differ between Groups 1 and 2.
CONCLUSIONSIn isolated rat hearts, propofol can improve cardiac functional recovery after ischemia-reperfusion by upregulating NOS activity in the myocardium. The NO system may play an important role in the preservation of myocardial ischemia-reperfusion injury produced by propofol.
Animals ; Coronary Circulation ; drug effects ; Enzyme Activation ; drug effects ; Heart ; drug effects ; Heart Function Tests ; Hypnotics and Sedatives ; pharmacology ; therapeutic use ; Immunohistochemistry ; In Vitro Techniques ; Male ; Myocardial Reperfusion Injury ; drug therapy ; enzymology ; Myocardium ; enzymology ; Nitric Oxide Synthase ; metabolism ; Propofol ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley
10.Effect of Shengmai Injection on cardiac function and inflammatory reaction in patients with acute coronary syndrome.
Ya-chen ZHANG ; Rui-ming CHEN ; Bao-jing LU ; Ye-zhi RONG
Chinese journal of integrative medicine 2008;14(2):107-110
OBJECTIVETo confirm the effect of Shengmai Injection (, SMI) in improving cardiac function in patients with acute coronary syndrome (ACS) and to explore its influence on inflammatory reaction in patients.
METHODSNinety ACS patients were randomized into two groups, the control group treated with conventional therapy and the SMI group treated with SMI. The patients' cardiac function was noted and the content of high sensitive C-reactive protein (hs-CRP) in venous blood was measured before treatment and 1 week and 3 weeks after treatment, so as to observe and compare their changes between the two groups.
RESULTSThe cardiac output, stroke volume and ejection fraction in the SMI group after 3 weeks of treatment were all higher than those in the control group (P<0.05). The serum content of hs-CRP was reduced in both groups (P<0.05), but the reduction in the SMI group was more significant than that in the control group (P<0.05).
CONCLUSIONSMI could improve the cardiac function and further inhibit the inflammatory reaction in patients with ACS.
Acute Coronary Syndrome ; drug therapy ; physiopathology ; C-Reactive Protein ; analysis ; Drug Combinations ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; therapeutic use ; Female ; Heart Function Tests ; drug effects ; Hemodynamics ; drug effects ; Humans ; Inflammation ; drug therapy ; Injections ; Male ; Middle Aged ; Ventricular Function, Left ; drug effects

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